Title: Development of a Photoacoustic Quantitative Ultrasound (PAQUS) device for clinical use Abstract: The objective of this program is to develop a highly innovative bone assessment device by combining our recently invented photoacoustic physio-chemical analysis (PAPCA) technique with more established quantitative ultrasound (QUA) techniques. After a clinic-ready Photoacoustic Quantitative Ultrasound (PAQUS) prototype device is fabricated by modifying a FDA approved QUS bone system, a targeted correlation study will be performed between the PAPCA function and the QUS function through an experiment on human subjects. The PAPCA technique was invented by Xueding Wang, PhD and his team at the University of Michigan (U-M). For a target bone, such as distal radius or calcaneus, a 2D physio-chemical spectrogram (PCS) is generated by conducting ultrasonic spectral analysis of the radio-frequency (RF) photoacoustic (PA) signals from the bone over a broad optical spectrum. PCS presents the ?optical signature? and the ?ultrasound signature? of the bone simultaneously in one 2D map. The map contains rich diagnostic information and allows quantitative analysis of the concentrations and, more importantly, the histological microstructures of trabecular bone, thus providing unique and clinically relevant information to the clinician. For example, smaller trabeculae, such as those found in osteoporotic bone, result in PA signals with higher frequency components. In addition to the evaluation of bone mass and bone quality, the proposed PAQUS device holds promise for accessing additional molecular and biochemical information. Comprehensive assessment of bone using PAPCA could lead to entirely new clinical approaches for screening, diagnosis, and treatment monitoring of osteoporosis. During this funding period, a commercially available QUS system, the GE Achilles Express, will be modified without affecting its original functions so that the same system can perform both PA and US measurements of a target bone simultaneously. By utilizing the Achilles Express, the two models can be directly compared on identically located physiology. Following modification and in-vitro testing, the system will be taken to U-M where a study on 10-20 human subjects will be performed. These results will be analyzed to determine the viability of a commercial device. This work will be performed cooperatively between IF LLC and U-M. IF is owned and operated by former GE Achilles product manager and senior scientist, Rich Morris. Mr. Morris, holder of over 15 QUS patents, including novel QUS transducer designs, was responsible for the introduction of the GE/Lunar Express and InSight QUS bone densitometers. The combination of the innovative technology and clinical access provided by the U-M with proven product development and QUS expertise of IF greatly improves the likelihood of commercialization of the proposed PAQUS bone assessment device.